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EC number: 457-470-9 | CAS number: 407-64-7
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2000
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: study performed under GLP and in accordance with OECD-/EU-testing guidelines
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Repeated Dose 28-day Oral Toxicity Study Regulation of Czech Ministry of Health No.251/1998 (identical with method B.7 Repeated dose (28 days) toxicity (oral) Directive 67/548/EEC)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Details on test material:
- - Name of test material (as cited in study report): 4-Trimethylaminobutyrobetain
- Molecular formula: C7H1SN02
- Physical state: liquid
- Stability under test conditions: yes
- Storage condition of test material: at room temperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: TOP VELAZ, STO., závod Koleč
- Age at study initiation: 6 weeks
- Housing: group housing à 6 animals per sex and concentration
- Diet (e.g. ad libitum): Futtermittel-Mühle Kocanda, Jesenice u Prahy
- Water (e.g. ad libitum): tap water
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 h darkness; 12 h continuous light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- 6 animals per sex and group were treated with the test item solution
- Duration of treatment / exposure:
- Test duration: 28 days
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0 mg/kg/day
Basis:
nominal in water
- Remarks:
- Doses / Concentrations:
250 mg/kg/day
Basis:
nominal in water
- Remarks:
- Doses / Concentrations:
500 mg/kg/day
Basis:
nominal in water
- Remarks:
- Doses / Concentrations:
1000 mg/kg/day
Basis:
nominal in water
- No. of animals per sex per dose:
- MALES
- 6 animals: 0 mg/kg/day
- 6 animals: 250 mg/kg/day
- 6 animals: 500 mg/kg/day
- 6 animals: 1000 mg/kg/day
FEMALES
- 6 animals: 0 mg/kg/day
- 6 animals: 250 mg/kg/day
- 6 animals: 500 mg/kg/day
- 6 animals: 1000 mg/kg/day - Control animals:
- yes
- Positive control:
- Control animals at 0 and 1000 mg/kg/day
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- The substance stimulates the general growth of animals (males and females). The substance increases the grip strength (only males, dose 250 mg/kg).
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- The substance stimulates the general growth of animals (males and females). The substance increases the grip strength (only males, dose 250 mg/kg).
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- See results section
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Decreased levels: ALP (only males), creatinine; increased levels: potassium (only females).
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- See results section
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- See results sectio
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- HEMATOLOGY
1. Dose concentrations of 500 and 1000 mg/kg/day:
Damage of red blood components (both sex, irreversible processes):
- Decreased levels: Total number of red blood cells, the level of blood colour, hematokrit.
Damage of white blood components (both sex):
- Decreased levels: Total number of white blood cells, total amount of neutrofil segments.
- Decreased number of blood platelets (both sex, reversible process).
2. Dose concentration 250 mg/kg/day :
No substantial changes.
EFFECTS IN ORGANS
1. Dose concentrations of 500 and 1000 mg/kg/day:
- Decreased weight of thymus and increased weight of testes (reversible process). at 500 and 1000 mg/kg/day
- Increased steatosis of hepathocytes in males (reversible process). at 500 and 1000 mg/kg/day
- Desquamation of embryonal epithelium of testes (reversible process).
- Increased incidence of pigment in spleen of females (reversible process).
- Slight increase of areactive necrosis of villi apexis in small intestine.
2. Dose concentration 250 mg/kg/day:
- No substantial changes
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 250 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Dose descriptor:
- NOEL
- Effect level:
- < 250 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The NOAEL of the aqueous solution on WISTAR rats was found to be 250 mg/kg/day, whereas the NOEL was determined to be < 250 mg/kg/day.
- Executive summary:
The test was performed 2000 under GLP according to the method Repeated Dose 28-day Oral Toxicity Study Regulation of Czech Ministry of Health No.251/1998 (identical with method B.7 Repeated dose (28 days) toxicity (oral) Directive 67/548/EEC). The study was performed on 6 male and 6 female Wistar rats at dose concentrations of 0, 250, 500 and 1000 mg/kg/day. There were neither mortality nor significant clinical symptoms observed. There were a couple of effects in hematological and biochemical parameters as well as some findings in organs at necropsy.
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